BENIGN PROSTATIC HYPERPLASIA (BPH)
Benign prostatic hyperplasia (BPH) is a common problem that affects the quality of life in approximately one third of men older than 50 years. BPH is histologically evident in up to 90% of men by age 85 years. As many as 14 million men in the United States have symptoms of BPH.(1) Worldwide, approximately 30 million men have symptoms related to BPH.
The prevalence of BPH in white and African-American men is similar. However, BPH tends to be more severe and progressive in African-American men, possibly because of the higher testosterone levels, 5-alpha-reductase activity, androgen receptor expression, and growth factor activity in this population. The increased activity leads to an increased rate of prostatic hyperplasia and subsequent enlargement and its sequelae.
According to a report, the overall incidence rate was 15 per 1000 man-years. The incidence increased linearly with age from three cases per 1000 man-years at the age of 45-49 year to a maximum of 38 cases per 1000 man-years at the age of 75-79 years. After the age of 80 years, the incidence rate remained constant. For a symptom-free man of 46 years, the risk to develop Lower Urinary Tract Syndrome (LUTS)/BPH over the coming 30 years, if he survives, is 45%. The overall prevalence of LUTS/BPH was 10.3%. The prevalence rate was lowest among males 45-49 years of age (2.7%) and increased with age until a maximum at the age of 80 years (24%).(2)
Pakistan with as many as 50% of the 2 million men older than 65 year are at risk of bladder outlet obstruction from BPH.(3)
Prostatic enlargement depends on the potent androgen dihydrotestosterone (DHT). In the prostate gland, type II 5-alpha-reductase metabolizes circulating testosterone into DHT, which works locally, not systemically. DHT binds to androgen receptors in the cell nuclei, potentially resulting in BPH.
In vitro studies have shown that large numbers of alpha-1-adrenergic receptors are located in the smooth muscle of the stroma and capsule of the prostate, as well as in the bladder neck. Stimulation of these receptors causes an increase in smooth-muscle tone, which can worsen Lower urinary tract symptoms (LUTS). Conversely, blockade of these receptors can reversibly relax these muscles, with subsequent relief of LUTS.
Microscopically, BPH is characterized as a hyperplastic process. The hyperplasia results in enlargement of the prostate that may restrict the flow of urine from the bladder, resulting in clinical manifestations of BPH. The prostate enlarges with age in a hormonally dependent manner. Notably, castrated males (i.e. who are unable to make testosterone) do not develop BPH.
The traditional theory behind BPH is that, as the prostate enlarges, the surrounding capsule prevents it from radially expanding, potentially resulting in urethral compression. However, obstruction-induced bladder dysfunction contributes significantly to LUTS. The bladder wall becomes thickened, trabeculated, and irritable when it is forced to hypertrophy and increase its own contractile force.
This increased sensitivity (detrusor overactivity [DO]), even with small volumes of urine in the bladder, is believed to contribute to urinary frequency and LUTS. The bladder may gradually weaken and lose the ability to empty completely, leading to increased residual urine volume and, possibly, acute or chronic urinary retention.
In the bladder, obstruction leads to smooth-muscle-cell hypertrophy. Biopsy specimens of trabeculated bladders demonstrate evidence of scarce smooth-muscle fibers with an increase in collagen. The collagen fibers limit compliance, leading to higher bladder pressures upon filling. In addition, their presence limits shortening of adjacent smooth muscle cells, leading to impaired emptying and the development of residual urine.
The main function of the prostate gland is to secrete an alkaline fluid that comprises approximately 70% of the seminal volume. The secretions produce lubrication and nutrition for the sperm. The alkaline fluid in the ejaculate results in liquefaction of the seminal plug and helps to neutralize the acidic vaginal environment.
The prostatic urethra is a conduit for semen and prevents retrograde ejaculation (i.e. ejaculation resulting in semen being forced backwards into the bladder) by closing off the bladder neck during sexual climax. Ejaculation involves a coordinated contraction of many different components, including the smooth muscles of the seminal vesicles, vasa deferentia, ejaculatory ducts, and the ischiocavernosus and bulbocavernosus muscles.
In a small percentage of men, untreated BPH can cause acute urinary retention, recurrent urinary tract infections, hydronephrosis, and even renal failure. It is estimated that a 60 year old man with moderate-to-severe symptoms would have a 13.7 percent chance of developing acute urinary retention in the following 10 years. Age, symptoms, urinary flow rate, and prostate volume are risk factors for acute urinary retention at least in population-based studies, though not in all clinical trials.(4) Men with symptomatic BPH who are not treated have about a 2.5 percent per-year risk of developing acute urinary retention.(5,6)
The natural history of BPH has been examined both in population-based studies and by looking at outcomes in the placebo arms of clinical trials. However, studies have found that outcomes among patients in the placebo arms of clinical trials may not accurately reflect outcomes in the general population.(7) In clinical trials, measurements of LUTS and peak urine flow tend to show a regression to the mean; whereas, this is not seen with measurements of prostate volume and Prostate-specific antigen (PSA).(8) A systematic review of the placebo arms of 16 randomized trials of medical treatment lasting for one to four years found that the risk of surgery ranged from 1 to 10 percent, and the risk of acute urinary retention ranged from 0.4 to 6.0 percent.(9) Patients experience some progression in symptoms, increase in prostate volume, and decrease in peak urine flow rate that can result in a need for invasive treatment.
SIGN AND SYMPTOMS
Symptoms often attributed to BPH can be caused by other disease processes, and a history and physical examination are essential in ruling out other etiologies of lower urinary tract symptoms (LUTS).
When the prostate enlarges, it may act like a "clamp on a hose," constricting the flow of urine. Nerves within the prostate and bladder may also play a role in causing the following common symptoms:
- Urinary frequency - The need to urinate frequently during the day or night (nocturia), usually voiding only small amounts of urine with each episode
- Urinary urgency - The sudden, urgent need to urinate, owing to the sensation of imminent loss of urine without control
- Hesitancy - Difficulty initiating the urinary stream; interrupted, weak stream
- Incomplete bladder emptying - The feeling of persistent residual urine, regardless of the frequency of urination
- Straining - The need strain or push (Valsalva maneuver) to initiate and maintain urination in order to more fully evacuate the bladder
- Decreased force of stream - The subjective loss of force of the urinary stream over time
- Dribbling - The loss of small amounts of urine due to a poor urinary stream
A sexual history is important, as epidemiologic studies have identified LUTS as an independent risk factor for erectile dysfunction and ejaculatory dysfunction.
Digital rectal examination
The digital rectal examination (DRE) is an integral part of the evaluation in men with presumed BPH. During this portion of the examination, prostate size and contour can be assessed, nodules can be evaluated, and areas suggestive of malignancy can be detected.
- Urinalysis - Examine the urine using dipstick methods and / or via centrifuged sediment evaluation to assess for the presence of blood, leukocytes, bacteria, protein, or glucose.
- Urine culture - This may be useful to exclude infectious causes of irritative voiding and is usually performed if the initial urinalysis findings indicate an abnormality.
- Prostate-specific antigen - Although BPH does not cause prostate cancer, men at risk for BPH are also at risk for this disease and should be screened accordingly (although screening for prostate cancer remains controversial).
- Electrolytes, blood urea nitrogen (BUN), and creatinine - These evaluations are useful screening tools for chronic renal insufficiency in patients who have high postvoid residual (PVR) urine volumes; however, a routine serum creatinine measurement is not indicated in the initial evaluation of men with lower urinary tract symptoms (LUTS) secondary to BPH.
Ultrasonography (abdominal, renal, transrectal) is useful for helping to determine bladder and prostate size and the degree of hydronephrosis (if any) in patients with urinary retention or signs of renal insufficiency. Generally, they are not indicated for the initial evaluation of uncomplicated LUTS.
Endoscopy of the lower urinary tract
Cystoscopy may be indicated in patients scheduled for invasive treatment or in whom a foreign body or malignancy is suspected. In addition, endoscopy may be indicated in patients with a history of sexually transmitted disease (e.g. gonococcal urethritis), prolonged catheterization, or trauma.
The severity of BPH can be determined with the International Prostate Symptom Score (IPSS) / American Urological Association Symptom Index (AUA-SI) plus a disease-specific quality of life (QOL) question. Questions on the AUA-SI for BPH concern the following:
- Incomplete emptying
- Weak stream
- Flow rate - Useful in the initial assessment and to help determine the patient’s response to treatment.
- PVR urine volume - Used to gauge the severity of bladder decompensation; it can be obtained invasively with a catheter or noninvasively with a trans abdominal ultrasonic scanner.
- Pressure flow studies - Findings may prove useful for evaluating for Bladder Outlet Obstruction (BOO).
- Urodynamic studies - To help distinguish poor bladder contraction ability (detrusor underactivity) from BOO.
- Cytologic examination of the urine - May be considered in patients with predominantly irritative voiding symptoms.
Watchful waiting is the recommended strategy for patients with benign prostatic hyperplasia (BPH) who have mild symptoms (International Prostate Symptom Score / American Urological Association Symptom Index [IPSS/AUA-SI] score ≤7) and for those with moderate-to-severe symptoms (IPSS/AUA-SI score ≥8) who are not bothered by their symptoms and are not experiencing complications of BPH. In those patients, medical therapy is not likely to improve their symptoms and/or quality of life (QOL).
In addition, the risks of treatment may outweigh any benefits in such cases. Patients managed expectantly with watchful waiting are usually re-examined annually.
Transurethral resection of the prostate (TURP) has long been accepted as the criterion standard for relieving bladder outlet obstruction (BOO) secondary to BPH. In current clinical practice, most patients with BPH do not present with obvious surgical indications; instead, they often have milder lower urinary tract symptoms (LUTS) and, therefore, are initially treated with medical therapy.
The era of medical therapy for BPH dawned in the mid-1970s with the use of nonselective alpha-blockers such as phenoxybenzamine. The medical therapeutic options for BPH have evolved significantly over the last 3 decades, giving rise to the receptor-specific alpha-blockers that comprise the first line of therapy.
Life style modifications
Data from the Prostate Cancer Prevention Trial revealed that a diet low in fat and red meat and high in protein and vegetables may reduce the risk of symptomatic BPH. Additionally, regular alcohol consumption was associated with a reduced risk of symptomatic BPH, but this is to be interpreted cautiously, given the untoward effects of excessive alcohol consumption.(10)
Phenoxybenzamine: Phenoxybenzamine is a nonselective alpha-adrenergic receptor blocker that antagonizes both alpha-1 and alpha-2 receptors. This non-selectivity leads to a higher incidence of adverse effects, which has led to decreased use of this agent in clinical settings. Phenoxybenzamine induces subjective improvement in urinary flow rates when compared with placebo. It may improve daytime and nighttime urinary frequency. Symptoms improve in 75% of patients.
Prazosin: Prazosin is currently approved for the treatment of hypertension. Prazosin improves urine flow rates by relaxing smooth muscle. Relaxation is produced by blocking alpha-1 adrenoreceptors in the bladder neck and prostate. The advantage of prazosin over nonselective alpha-adrenergic blockers includes a lower incidence of adverse effects. Because of availability of longer-acting, once-daily selective agents, however, the clinical utility of prazosin for BPH has been reduced.
Prazosin improves urinary flow rate and frequency of micturition. Subjective improvement is observed in 82% of patients treated. When increasing dosages, administer the first dose of each increment at bedtime to reduce syncopal episodes. Although doses above 20 mg/d do not usually increase efficacy, some patients may benefit from up to 40 mg/d.
Alfuzosin: Alfuzosin is indicated for the treatment of the signs and symptoms of BPH. Alfuzosin is an alpha-1 blocker of adrenoreceptors in the prostate. Blockade of adrenoreceptors may cause smooth muscles in the bladder neck and prostate to relax, resulting in improvement in urine flow rate and reduction in symptoms of BPH.
Terazosin: Terazosin is a quinazoline compound that counteracts alpha1-induced adrenergic contractions of bladder neck, facilitating urinary flow in the presence of BPH. It is indicated for the treatment of symptomatic BPH and hypertension. Its effect on voiding symptoms and flow rates is dose-dependent. It improves irritative and obstructive voiding symptoms. Improvement in flow rate is objective.
Tamsulosin: Tamsulosin is indicated for the treatment of the signs and symptoms of BPH. It is an alpha-adrenergic blocker specifically targeted to alpha-1 receptors. Tamsulosin has the advantage of producing relatively less orthostatic hypotension; it requires no gradual up-titration from the initial dosage. It inhibits postsynaptic alpha-adrenergic receptors, resulting in vasodilation of veins and arterioles and a decrease in total peripheral resistance and blood pressure. It improves irritative and obstructive voiding symptoms.
Silodosin: Silodosin is indicated for the treatment of the signs and symptoms of BPH. Silodosin selectively antagonizes postsynaptic alpha1-adrenergic receptors in the prostate, bladder base, prostatic capsule, and prostatic urethra. This action induces smooth muscle relaxation and improves urine flow.
Finasteride: Finasteride is indicated for the treatment of symptomatic BPH in men with an enlarged prostate. When combined with doxazosin, it can also reduce the risk of symptomatic progression of BPH. Finasteride inhibits conversion of testosterone to DHT, causing serum DHT levels to decrease. It is beneficial in men with prostates larger than 40 g and can improve symptoms and reduce prostatic size by 20-30%. Reduction in prostate size is sustained for 5 years following treatment. Finasteride improves urinary flow rate by 2 mL/s.
Dutasteride: Dutasteride is indicated for the treatment of BPH as monotherapy or in combination with tamsulosin. Dutasteride improves symptoms, reduces urinary retention, and may decrease the need for BPH-related surgery. It inhibits 5 alpha-reductase isoenzymes types I and II. This agent suppresses conversion of testosterone to DHT by more than 95%, causing serum DHT levels to decrease.
PDE5 selective inhibitor: Inhibition of PDE5 increases cGMP activity, which increases vasodilatory effects of nitric oxide. Sexual stimulation is necessary to activate response. Tadalafil has been approved by the FDA for the treatment of BPH signs and symptoms.
PDE5 inhibition has been shown to induce smooth muscle relaxation in the lower urinary tract. It has also been approved for the treatment of simultaneous BPH and Erectile Dysfunction (ED).
Increased sensitivity for erections may last 36 h with intermittent dosing. Low-dose daily dosing may be recommended for more frequent sexual activity (i.e. twice weekly); men can attempt sexual activity at any time between daily doses.
TURP is considered the criterion standard for relieving BOO secondary to BPH. The indications to proceed with a surgical intervention include the following:
- Acute Urinary Retention (AUR)
- Failed voiding trials
- Recurrent gross hematuria
- Urinary tract infection
- Renal insufficiency secondary to obstruction
Additional indications for surgical intervention include failure of medical therapy, a desire to terminate medical therapy, and/or financial constraints associated with medical therapy. However, TURP carries a significant risk of morbidity (18%) and mortality risk (0.23%).
TURP is performed with regional or general anesthesia and involves the placement of a working sheath in the urethra through which a hand-held device with an attached wire loop is placed. High-energy electrical cutting current is run through the loop so that the loop can be used to shave away prostatic tissue. The entire device is usually attached to a video camera to provide vision for the surgeon.
Although TURP is often successful, it has some drawbacks. When prostatic tissue is cut away, significant bleeding may occur, possibly resulting in termination of the procedure, blood transfusion, and a prolonged hospital stay. Patients are usually monitored overnight and discharged the following morning, with or without a catheter.
Irrigating fluid may also be absorbed in significant quantities through veins that are cut open, with possible serious sequelae termed transurethral resection syndrome (TUR syndrome). However, this is very rare and does not occur with saline irrigation used in bipolar devices. A urinary catheter must be left in place until the bleeding has mostly cleared.
The large working sheath combined with the use of electrical energy may also result in stricturing of the urethra.
The cutting of the prostate may also result in a partial resection of the urinary sphincteric mechanism, causing the muscle along the bladder outlet to become weak or incompetent. As a result, when the patient ejaculates, this sphincteric mechanism cannot keep the bladder adequately closed. The ejaculate consequently goes backwards into the bladder (i.e. retrograde ejaculation), rather than out the penis. Additionally, if the urinary sphincter is damaged, urinary incontinence may result.
The nerves associated with erection run along the outer rim of the prostate, and the high-energy current and/or heat generated by such may damage these nerves, resulting in impotence.
Minimally invasive treatment
There is considerable interest in the development of other therapies to decrease the amount of obstructing prostate tissue while avoiding the above-mentioned adverse effects associated with TURP. These therapies are collectively called minimally invasive therapies.
Transurethral incision of the prostate: Transurethral incision of the prostate (TUIP) has been in use for many years and, for a long time, was the only alternative to TURP. It may be performed with local anesthesia and sedation. TUIP is suitable for patients with small prostates and for patients unlikely to tolerate TURP well because of other medical conditions. TUIP is associated with less bleeding and fluid absorption than TURP. It is also associated with a lower incidence of retrograde ejaculation and impotence than TURP.
Lasers deliver heat to the prostate in various ways. Lasers heat prostate tissue, causing tissue death by coagulative necrosis, with subsequent tissue contraction; however, laser coagulation of the prostate in this specific sense has met with limited results.
Lasers have also been used to directly evaporate, or to melt away, prostate tissue, which is more effective than laser coagulation. Photoselective vaporization of the prostate produces a beam that does not directly come into contact with the prostate; rather, it delivers heat energy into the prostate, resulting in destruction/ablation of the prostate tissue.
Potassium-titanyl-phosphate (KTP) and holmium lasers are used to cut and/or enucleate the prostate, similar to the TURP technique. These are widely used laser techniques.
Transurethral vaporization / ablation with the KTP or holmium laser can be performed with general or spinal anesthesia and can be performed in an outpatient setting. Catheter time usually lasts less than 24 hours. Studies suggest that photo selective vaporization of the prostate can significantly improve and sustain symptomatic and urodynamic outcomes.
This procedure has been quite useful in patients who require anticoagulation for various medical conditions, since anticoagulation does not need to be interrupted for this procedure, thus further decreasing patient risk.(11, 12)
Lasers may be used in a knifelike fashion to directly cut away prostate tissue (i.e. holmium laser enucleation of the prostate), similar to a TURP procedure. The holmium laser allows for simultaneous cutting and coagulation, making it quite useful for prostate resection. Laser enucleation of the prostate has proved to be safe and effective for treatment of symptomatic BPH, regardless of prostate size, with low morbidity and short hospital stay.
TUR syndrome is not seen with this technique, because iso-osmotic saline is used for irrigation. Additionally, removed prostatic tissue is available for histologic evaluation, whereas vaporization / ablation technique does not provide tissue for evaluation. Holmium laser enucleation of the prostate may prove to be the new criterion standard for surgical management of BPH.(13, 14)
Laser treatment usually results in decreased bleeding, fluid absorption, and length of hospital stay, as well as decreased incidence of impotence and retrograde ejaculation when compared with standard TURP. However, healing from laser treatment does not occur until after a period when dead cells slough; thus, patients may experience urinary urgency or irritation, resulting in frequent or uncomfortable urination for a few weeks.
The results of laser therapy vary from one another because not all wavelengths yield the same tissue effects. For example, interstitial lasers (e.g. indigo lasers) are designed to heat tissue within the confines of the prostate gland and spread radiant energy at relatively low energy levels. They do not directly involve the urethral portion; thus, irritative symptoms following the procedure are potentially reduced.
Contact lasers such as KTP or holmium, on the other hand, are designed to cut and vaporize at extremely high temperatures. They usually bring about more relief of urinary symptoms than treatment with medicines, but not always as much as is provided with TURP. However, KTP laser vaporization and holmium laser enucleation yield results that rival those of TURP.
Transurethral microwave therapy: The use of microwave energy, termed transurethral microwave therapy (TUMT), delivers heat to the prostate via a urethral catheter or a transrectal route. The surface closest to the probe (the rectal or urethral surface) is cooled to prevent injury. The heat causes cell death, with subsequent tissue contraction, thereby decreasing prostatic volume.
TUMT can be performed in the outpatient setting with local anesthesia. Microwave treatment appears to be associated with significant prostatic swelling; a considerable number of patients require a urinary catheter until the swelling subsides. In terms of efficacy, TUMT places between medical therapy and TURP. The 2010 AUA guidelines state TUMT is an effective option for partially relieving symptoms that may be considered in patients with moderate or severe LUTS secondary to BPH.(15)
Transurethral needle ablation of the prostate: Transurethral needle ablation of the prostate (TUNA) involves using high-frequency radio waves to produce heat, resulting in a similar process of thermal injury to the prostate as previously described. A specially designed transurethral device with needles is used to deliver the energy.
TUNA can be performed under local anesthesia, allowing the patient to go home the same day. Similar to microwave treatment, radiofrequency treatment is quite popular, and a number of urologists have experience with its use. Radiofrequency treatment appears to reliably result in significant relief of symptoms and better urine flow, although not quite to the extent achieved with TURP. The 2010 AUA guideline update considers TURP an appropriate and effective treatment option for moderate or severe LUTS.
High-intensity ultrasound energy therapy: High-intensity ultrasound energy therapy delivers heat to prostate tissue, with the subsequent process of thermal injury. High-intensity ultrasound waves may be delivered rectally or extracorporeally and can be used with the patient on intravenous sedation. Urinary retention appears to be common with its use.
High-intensity ultrasound energy also produces moderate results in terms of improvement of the urinary flow rate and urinary symptoms, although its use is now relatively limited compared with the more popular TUNA and TUMT.
High-intensity ultrasound is considered investigational at this time and should not be offered outside of clinical trials.
Mechanical approaches: Mechanical approaches are used less commonly and are usually reserved for patients who cannot have a formal surgical procedure. Mechanical approaches do not involve the use of energy to treat the prostate.
Prostatic stents are flexible devices that can expand when put in place to improve the flow of urine past the prostate. Complications associated with their use include encrustation, pain, incontinence, and overgrowth of tissue through the stent, possibly making their removal quite difficult.
In September 2013, the FDA authorized the marketing of the first permanent implant to relieve low or blocked urine flow in men aged 50 years and older with an enlarged prostate. The UroLift system relieves urine flow by pulling back prostate tissue that is pressing on the urethra. Approval was based on 2 studies of 274 men with BPH implanted with 2 or more UroLift sutures. The UroLift was successfully inserted in 98% of participants, and a 30% increase in urine flow and a steady amount of residual urine in the bladder was observed. Patients reported fewer symptoms and improved quality of life in the 2 years following device implantation.
The incidental discovery that the use of selective prostatic arty embolization (PAE) to control bleeding secondary to BPH resulted in improved LUTS led to investigation of its direct use in the relief of LUTS in patients with BPH. Although a growing body of evidence supports its safety and efficacy, PAE has yet to be established as a standard-of-care treatment option. A systematic review that included 16 studies concluded that PAE should still be considered experimental.
GOALS OF THERAPY
The goals of pharmacotherapy for benign prostatic hyperplasia (BPH) are to reduce morbidity and to prevent complications. The agents used include alpha-adrenergic blockers, 5-alpha-reductase inhibitors, and various combinations.
Treatment for BPH is based on guidelines from the prestigious societies such as American urological association (AUA)
To view the AUA guidelines, click on the following link
LONG TERM MONITORING
Patients with BPH who have symptoms significant enough to be placed on medication should be evaluated during office visits to discuss the efficacy of the medication and potential dose adjustment. These visits should take place at least biannually. Patients should undergo prostate cancer screening at least annually.
CONSULTATION AND COUNSELING
There is no known way to prevent prostate enlargement. It is a common part of aging.
- Avoid drinking liquids after 6 p.m. to reduce the need to urinate frequently during the night.
- Drinking more fluid, up to eight glasses of water per day, may help prevent infection. However, for men already suffering with increased urinary frequency, this may only exacerbate the problem. In most cases, drinking a normal amount of fluid based on thirst is all that is necessary.
- There is evidence that cranberry juice may be helpful in the prevention of urinary tract infections in those who are prone to developing these.
To help control the symptoms of an enlarged prostate, offer following advices to patient:
- Limit beverages in the evening.Don't drink anything for an hour or two before bedtime to avoid middle-of-the-night trips to the toilet.
- Limit caffeine and alcohol.They can increase urine production, irritate the bladder and worsen symptoms.
- Limit decongestants or antihistamines.These drugs tighten the band of muscles around the urethra that control urine flow, making it harder to urinate.
- Go when you first feel the urge.Waiting too long might overstretch the bladder muscle and cause damage.
- Schedule bathroom visits.Try to urinate at regular times — such as every four to six hours during the day — to "retrain" the bladder. This can be especially useful if you have severe frequency and urgency.
- Follow a healthy diet.Obesity is associated with enlarged prostate.
- Stay active.Inactivity contributes to urine retention. Even a small amount of exercise can help reduce urinary problems caused by an enlarged prostate.
- Urinate — and then urinate again a few moments later. This practice is known as double voiding.
- Keep warm.Colder temperatures can cause urine retention and increase the urgency to urinate.(16)
- McVary KT, Roehrborn CG, Avins AL, Barry MJ, Bruskewitz RC, Donnell RF, et al. Update on AUA Guideline on the Management of Benign Prostatic Hyperplasia.J Urol. 2011 Mar 17.
- Verhamme, K; Dieleman, JP; Bleumink, GS; Van Der Lei, J; Sturkenboom, MC; Artibani, W; Begaud, B; Berges, R et al. (2002). "Incidence and Prevalence of Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia in Primary Care— the Triumph Project". European J Urology 42 (4): 323–8.
- Condie JD Jr., Cutherell L, Mian A. Suprapubic prostatectomy for benign prostatic hyperplasia in rural Asia: 200 consecutive cases. Urology. 1999;54:1012-6.
- O'Leary MP, Wei JT, Roehrborn CG, et al. Correlation of the International Prostate Symptom Score bother question with the Benign Prostatic Hyperplasia Impact Index in a clinical practice setting. BJU Int 2008; 101:1531.
- Barry M, Roehrborn C. Management of benign prostatic hyperplasia. Annu Rev Med 1997; 48:177.
- Marberger MJ, Andersen JT, Nickel JC, et al. Prostate volume and serum prostate-specific antigen as predictors of acute urinary retention. Combined experience from three large multinational placebo-controlled trials. Eur Urol 2000; 38:563.
- Roberts RO, Lieber MM, Jacobson DJ, et al. Limitations of using outcomes in the placebo arm of a clinical trial of benign prostatic hyperplasia to quantify those in the community. Mayo Clin Proc 2005; 80:759.
- Roehrborn CG. Definition of at-risk patients: baseline variables. BJU Int 2006; 97 Suppl 2:7.
- Emberton M, Fitzpatrick JM, Garcia-Losa M, et al. Progression of benign prostatic hyperplasia: systematic review of the placebo arms of clinical trials. BJU Int 2008; 102:981.
- Kristal AR, Arnold KB, Schenk JM, Neuhouser ML, Goodman P, Penson DF. Dietary patterns, supplement use, and the risk of symptomatic benign prostatic hyperplasia: results from the prostate cancer prevention trial.Am J Epidemiol. 2008 Apr 15. 167(8):925-34.
- Malek RS, Kuntzman RS, Barrett DM. Photoselective potassium-titanyl-phosphate laser vaporization of the benign obstructive prostate: observations on long-term outcomes.J Urol. 2005 Oct. 174(4 Pt 1):1344-8.
- Kuntz RM. Laser treatment of benign prostatic hyperplasia.World J Urol. 2007 Jun. 25(3):241-7.
- Elzayat EA, Habib EI, Elhilali MM. Holmium laser enucleation of the prostate: a size-independent new "gold standard".Urology. 2005 Nov. 66(5 Suppl):108-13.
- Barry MJ, Cockett AT, Holtgrewe HL, et al. Relationship of symptoms of prostatism to commonly used physiological and anatomical measures of the severity of benign prostatic hyperplasia.J Urol. 1993 Aug. 150(2 Pt 1):351-8.
- Crane M. FDA OKs New Device to Treat BPH. Medscape Medical News. Available athttp://www.medscape.com/viewarticle/810981. Accessed: September 23, 2013.